Lung cancer is the most common cause of cancer deaths worldwide with more than 1.2 million people dying of the disease each year1,2. Only 16% of lung cancer patients survive 5 years or more because the majority of the patients are diagnosed with advanced incurable disease by the time they present with symptoms3. This is in marked contrast to the 5 year survival of 70-90% that can be achieved when lung cancer is diagnosed and treated at an earlier stage3-5. Early detection and treatment of lung cancer is a promising strategy to reduce lung cancer mortality.
Technologies such as spiral computed tomography (CT), autofluorescence bronchosocopy (AFB), and optical coherence tomography are already available and can detect lung cancers down to the sub-millimeter range6,7. Although these sophisticated technologies are very sensitive, they are not specific enough to allow practical or cost-effective application in identifying early lung cancer in the general population, or even in high-risk sub-groups because there is wide variation in lung cancer risk even among heavy smokers8. If we can apply a filter to identify smokers at the highest risk for lung cancer, the positive predictive value of screening tests such as spiral CT can be significantly improved 9,10.
Spiral CT is very sensitive but the false-positive rate is relatively high resulting in unnecessary or potentially harmful downstream investigations and/or treatment. Bronchoscopy under conscious sedation can detect early lung cancer in the central airways not visible by spiral CT and can allow cytologic, histologic or genomic diagnosis of lung cancer. However, it is comparatively more expensive and time consuming than spiral CT. In the context of a health care delivery system, these technologies need be used in a selective fashion.
A blood based biomarker is attractive as a filter because blood is easily accessible and measurements may be repeated over time. Several studies have identified potential proteomic biomarkers that are differentially expressed between patients with and without lung cancer11-13. No biomarker has yet been validated in screen-detected early lung cancers. Major impediments in the discovery of biomarkers for detection of asymptomatic lung cancer have included measurement of thousands of proteins simultaneously in tens of samples, resulting in false positives; 2) use of analytical methods that do not provide precise and accurate determination of potential tumor specific proteins that are expressed in much lower concentrations than other more abundant proteins resulting in false negatives14, 15, 16 and 3) a lack of access to blood samples collected in population based studies prior to clinical diagnosis of cancer for validation and replication.
There is an unmet need in the field for rapid, sensitive and accurate blood-based screening tests for the early detection of lung cancer, assessment of risk of developing lung cancer, and the monitoring of response after treatment with curative intent.